Efficacy and Safety of Oral Zavegepant in Migraine Prevention: A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study in Patients with Chronic Migraine.

INTRODUCTION

This study aimed to assess the efficacy and safety of once daily oral zavegepant as a preventive treatment for chronic migraine.

METHODS

This multicenter, randomized, double-blind, placebo-controlled phase 2/3 study consisted of a 12-week double-blind treatment (DBT) phase and a 52-week open-label extension (OLE). Adults with ≥ 1-year history of chronic migraine (with or without aura), ≥ 15 headache days/month, ≥ 8 migraine days/month, and ≥ 1 headache-free day/month during the 3 months prior to screening were randomly assigned 2:2:1:1 to zavegepant 100 mg, 200 mg, placebo for zavegepant 100 mg, or placebo for zavegepant 200 mg. Following a 28-day observation phase (OP), participants took the study treatment every calendar day. The primary endpoint was mean change from the OP in number of migraine days/month in the DBT phase. This study was stopped prematurely due to recruitment challenges.

RESULTS

Of 1753 screened participants, 522 were treated and 411 completed the DBT phase. Participants were predominantly female (n = 391, 79.5%) and mean (SD) age of chronic migraine onset was 26.5 (11.7) years. The mean (97.5% CI) changes from the OP in number of migraine days/month in the DBT phase were - 7.0 (- 8.10, - 5.92), - 6.3 (- 7.45, - 5.10), and - 5.6 (- 6.80, - 4.37) for zavegepant 100 mg, 200 mg, and placebo groups, respectively. The corresponding least squares (LS) mean change differences (zavegepant-placebo pooled; 97.5% CI) were - 1.4 (- 2.72, - 0.12) and - 0.7 (- 2.07, 0.69) for zavegepant 100 mg and zavegepant 200 mg groups, respectively. During DBT, 21 (12.1%) and 14 (8.0%) participants had at least one adverse event considered zavegepant-related in the zavegepant 100 mg and 200 mg groups, respectively, with corresponding rates of nine (5.8%) and nine (6.3%) participants during the OLE.

CONCLUSIONS

Oral zavegepant had a favorable safety and tolerability profile for up to 200 mg daily. Additional research is needed to determine the effectiveness of oral zavegepant as a preventive migraine treatment.

TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04804033.